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Therapy involving the replication and stability of chromosomes will hold many promising possibilities for the field of antiaging in the future.

The potential for skin rejuvenation is available via plant stem cell technology.

There remains a strong trend to further focus on sophisticated science and research in all aspects of product/ingredient development: novel ingredients of all origins, novel delivery systems, and novel ways to substantiate the claims with new techniques and methods.

The beauty industry, particularly since the inception of cosmeceuticals, is built on the principle of innovation. “Manufacturers use new innovation technologies to satisfy consumers’ growing needs, not only for high-quality, efficacious products, but also to provide an increasingly sophisticated blend of therapeutic, natural and eco-friendly ingredients,” says Linda Walker, CEO, CoValence Laboratories. Innovative ingredient concepts from many sources and directions are giving enhanced quality and function to products, with advances that seem far-fetched just around the corner, or even already on shelves.

“The industry is now focusing on new molecular biology strategies and advanced skin delivery systems to enhance the effect of their cosmetic products,” says Walker. Global skin care manufacturers have introduced or are researching a wide range of innovative products, especially in the antiaging and preventive aging segments, capitalizing on consumers’ desire to stay young, as well as the emergence of new science advances. From telomeres, sirtuins and nanotechnology to stem cells, epigenetics and cell-targeting technology, biotechnology is inspiring cosmetic chemists to develop some of the most revolutionary skin care in the history of the industry.

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Tissue repair—to reduce wrinkles and improve skin elasticity—via stimulation by designer peptides such as Sederma’s Matrixyl family, improved moisturizing mechanisms via osmotic regulation thus retarding senescence, the biology of aging, at the cellular level, protecting the skin against external aggression by supplying it with its own defense molecules and/or stimulating these systems topically. These are all pathways presently used or explored to slow the signs and symptoms of aging, and sometimes to help reversing some of the most visible ones. “Antiage research will be the main thrust of cosmetic laboratories for years to come,” says Lintner.

Telomeres

With the 2009 Nobel Prize of Physiology being awarded for telomere [the specialized chromosome structure involved in the replication and stability of the chromosome] research, there was much talk throughout 2009 of the potential for stabilizing telomere shortening and increasing cell life. All cells appear to have the gene that encodes an enzyme—called telomerase—capable of restoring shortened telomeres, the cell’s biological clock. The cells in which telomerase is active seem to be able to divide indefinitely.

In most normal cells, however, the activity of telomerase is somehow suppressed, so they cannot divide beyond a limited number, called the Hayflick limit or cellular senescence. When that happens, cells either die or enlarge, lose their function and slow down, hindering younger cells.

Basically, if the telomeres are shortened, cells age. Conversely, if telomerase activity is high, telomere length is maintained, and cellular senescence is delayed. A profound discovery when traditional thinking was to promote cell turnover to keep cells young. Even though knowledge of telomerase on human experiments is in its infancy, telomerase therapy will hold many promising possibilities for the field of antiaging in the future. The telomere-associated proteins sirtuins are a family of enzymes found naturally in the body that are said to prolong the life span of cells and slow the visible aging process as well. Resveratrol, the “wine compound,” has been around for years as a potent antioxidant and anti-inflammatory but got new buzz recently as a potential activator of sirtuins, increasing cell life.

One ingredient advancement is Renovage (Teprenone) from Sederma, which claims to stabilize telomere shortening, increasing cell life by one-third. Renovage also firms, hydrates, plumps and reduces the appearance of wrinkles, sun spots, redness and pores. Giving the company a head start in the preventive skin care market, the product targets younger consumers who are increasingly becoming aware of effective skin care from an earlier age and desiring products that will hold off the visual signs of aging.

Superfruits

While minimizing the cellular clock may be possible using genetic engineering, there are risks involved—especially so early in the understanding of how it works. It could possibly increase the risk of cancer or harm active, healthy cells. The simplest defense remains to be to avoid unnecessary cell divisions by minimizing exposure to factors that promote it—free radicals, inflammation, toxins and UV radiation. Antioxidants have the desired effect, but that’s not new.

The next generation of antioxidants, however, is new. Anthocyanins—a class of compounds called flavonoids—are water-soluble pigments found in colorful fruits, and act as powerful antioxidants helping to protect plants from UV damage. They are also part of a larger group of compounds called polyphenols, which have been shown to be strong antioxidants with potential health benefits. “Anthocyanins are botanically derived compounds that represent the next ‘super fruit’ class of phytochemical ingredients,” says Frank L. Jaksch Jr., co-founder and CEO of ChromaDex. “This novel and ‘green’ technology will enable suppliers to selectively and cost-effectively manufacture these ingredients and make them commercially available for the first time.”

Anthocyanins are only available as crude extracts—acai, bilberry, black currant, cranberry, for example—which can be expensive and inconsistent. And getting the pure extract from natural biomass is complicated. ChromaDex has been working on selective methods of manufacturing anthocyanins for more than eight years. The company has determined that a novel process of fermentation would be the most efficient and most sustainable way to produce isolated compounds rather than combinations of the compounds extracted from the plant. ChromaDex is completing the commercial development of the technology, first focusing on the production of cyanidin-3-O-glucoside (C-3-G).

Cyanidin, like other anthocyanidins, has supposed antioxidant and radial-scavenging effects that may protect cells from oxidative damage and can be used in cosmetic applications.

As we age, skin repair is indeed less efficient. However, the potential for skin rejuvenation is available via plant stem cell technology. “Plant stem cells can provide excellent beneficial support to the skin’s own stem cells,” says CoValence’s Walker. “They can produce higher concentrations of specific antioxidant and protein metabolites through eliciting factors like UV radiation or jasmonic acid [a plant hormone involved in growth inhibition and senescence] than the source plant, for example.”

Applications in cosmetics are widespread and—when used for purposes such as moisturizing, whitening, acne or rosacea treatments, radical scavenging, UV protec- tion, collagen promotion and revitalizing dull skin—can be very successful.

Adult stem cells located in some adult tissues can only differentiate into their own or related cell types. These cells act as a repair system for the body but also maintain the normal turnover of regenerative organs such as the skin. Epidermal stem cells replenish and maintain the balance of cells within the skin tissue and regenerate tissue damages during injury. But with age, the number of skin stem cells decreases and their ability to repair the skin becomes less efficient. In contrast to the human variety, plant cells are totipotent, meaning that every cell has the ability to regenerate new organs (leave, flower, seed, etc.) or even the whole plant. Besides, all plant cells can dedifferentiate and become a stem cell. All stem cells, independently of their origin (plant, animal or human) contain specific epigenetic factors whose function is to maintain the self-renewal capacity of stem cells.

Stem cells from a rare red grape variety provide the basis for Mibelle’s latest skin care ingredient the Swiss company claims can help protect human skin stem cells [For more information on Mibelle, read “Pushing Boundaries: Claims & Substantiation in Skin Care” in the April 2009 issue of GCI magazine. Also available online at www.GCImagazine.com]. The company claims Solar Vitis, a powder based on the stem cells of the Gamay Tenturier Fréaux grape, helps the skin stem cells maintain their characteristics and protects these essential cells against the stresses induced by UV, delaying senescence. According to Mibelle, these plant stem cells contain components and epigenetic factors that can protect human skin stem cells, in this case from UV radiation. The internal fluid of these plant cells contains components that help to protect and maintain the function of the human stem cells. This variety is one of the few red grapes that has red flesh and juice—the majority have red skin but white flesh and juice—which is due to the high quantity of anthocyanins in the fruit.

Normally congregating in the skin of the grape, the anthocyanins in the Gamay Tenturier Fréaux variety are also present in the flesh, leading to higher antioxidant levels overall, and explaining the red color. These antioxidants, along with other metabolites present in the grape, make it an excellent candidate for the company’s PhytoCellTec technology, which enables Mibelle to culture the plant cells in large quantities in the laboratory. The technology, developed in 2008, enables the company to breed cells in the laboratory from plants that are rare, protected, seasonal or otherwise unavailable.

To harvest the stem cells, the company first induces a wound in the plant, which causes the surrounding cells to dedifferentiate (turn back into stem cells) and form a wound-healing tissue called a callus.

Once the wound has healed, these cells can differentiate again and build new tissue. These callus cells are harvested by Mibelle, and can be cultivated on a large scale using a bioreactor system.

Solar Vitis is the second of Mibelle’s ingredients to be based on the PhtyoCellTec technology, following the use of a rare Swiss apple variety used in skin care brand 3Lab’s collection of antiaging creams and serums that stimulate the skin’s own stem cells to combat wrinkles.

According to Mibelle, plant cell culture technology can, theoretically, be used to propagate any plants in the form of cells, opening many possibilities for the future. The company has other products based on this technology in the pipeline.

Cell-targeting Technologies

Cell-targeting technologies are already popular in marketed applications. Products based on lipopeptides, such as Sederma’s Idealift, fall into this category. They are designed to interact with specific target cells for specific activities, enhanced with homing structures that allow them to reach their targets, according to Lintner. Idealift stimulates the synthesis of elastin and other proteins related to its formation, acting on the skin fibroblasts involved in the building of elastic tissue. The company’s in vitro tests showed an increase of more than 94% in the settling of elastin/tropoelastin in the extracellular matrix after Idealift had been administered to the fibroblasts.

The possibilities are almost endless. “The more we understand cellular interactions—by molecular biology studies and other in vitro techniques—the more potential targets we find for these novel substances: stimulating repair enzymes, inhibiting breakdown processes, improving inter-cell communication, protecting DNA and other vital structures in the cells are all strategies that are being explored and applied,” explains Lintner. CoValence’s recent innovations—such as Mitoprotect, advanced spin trap technology, plant stem cell ingredients and chiral technology—provide a wide range of free radical scavenging, skin cell protection and nourishment and wide range skin beneficial functions as well. Mitoprotect technology was developed with encapsulated ingredients to nourish and stimulate the mitochondrial support enzymes. Mitoprotect 2 will be introduced soon, as a companion to the original Mitoprotect. It is formulated with a unique combination of mitochondria protect ingredients, featuring plant stem cells that have been created and produced by the company.

Private label company YG Laboratories, Inc., will introduce Cell Youth Serum as a stock or custom product this month (March 2010). It is a cell-targeted emulsion that utilizes technology ranging from stem cell stimulation to prolonging cellular activity and postponing senescence. Because tissues and proteins of the body are manufactured in the cell, the company focuses on working with DNA—looking at epigenetic influences, helping to elongate the lifespan of a stem cell before it goes into senescence. “We can help the cell remain healthy and active longer by supporting the different processes that the cell uses naturally to protect and repair DNA, at the mitochondria level,” says Rebecca James Gadberry, CEO, YG Labs. “By targeting the cell, we are able to bring the cell back into a much more youthfully active state, allowing the skin that it produces to be more youthful and have better quality in appearance, texture and clarity.” The basic premise is to stimulate the natural antioxidant enzymes in the cell, rather than sending antioxidants into the cell to do its work.

Safety and Sustainability

Without sustainability, making greener choices is irrelevant because there wouldn’t be any plants left to utilize. Biological processes that use enzymes or other natural elements to create the reaction to manufacture specific ingredients allow high-tech to merge with natural. It’s also critical to have new natural formulating ingredient options for emulsifiers, preservatives, solvents, etc.

The plant stem cells from different plants can be produced by a biotechnological approach, for example, to provide large amounts of active principles for cosmetic use without destroying the entire plants. There is no concern necessary about endangered plant species. “Today’s products require constant inno

vations, continuously moving toward natural and sustainability, respecting the environment,” says Roberto Ascoli, Symrise. The ingredient supplier is one of many vendors who has taken steps to move in this direction, not only through its BioActives division—including the recent addition of Actipone superfruits—but with alternative processing and manufacturing. Ascoli suggests goals for the industry should be innovation that is safe for the consumer and fully respecting a life cycle concept—natural source, respecting biodiversity, biodegradable, sustainable, in renewable packaging and with a low carbon print. In a market driven more and more by consciousness, not marketing, there is an ever-growing concern for keeping the planet for your children. “[Notably] younger consumers have built this as part of an ethereal world being, which has become intrinsic in their purchase choices,” he explained.

YG Labs’ Gadberry also emphasizes that as the industry delves deeper into biotechnological advances, more testing is needed to ensure products are safe, not just from a U.S. Food and Drug Administration (FDA) standpoint. Targeting cells, be they stem cells or other types, one must always make sure of the absence of foreseeable risks; the more potent the substances, the more important this aspect becomes. “What we put on the human body, if it can penetrate and have cellular activity or cause a chemical to be released that has cellular activity, can affect the human genome,” she explains. With the study of epigenomes, how lifestyle choices and even the products you use can affect the way the genome is expressed, the industry is beginning to see how genetic expression can change not only in a person’s lifetime but in a few days or weeks. This impacts individuals and the planet, and therefore succeeding generations.

“We need to ensure that our products are safe, more so than according to the FDA or through one ingredient supplier,” says Gadberry. “The responsibility falls on us to ensure claims and validate safety.” Products tend to be tested as stand-alone items, but consumers have multiple exposures from more than one product in a single morning. On top of that, not all genomes are the same, so what’s safe to one person is not necessarily safe for another.

“As we look toward the future, we see a strong trend to further focus on sophisticated science and research in all aspects: novel ingredients of all origins, novel delivery systems, novel ways to substantiate the claims with new techniques and methods both in vitro and in vivo,” says Sederma’s Lintner. But first, stifling regulatory issues must be addressed. “The industry needs one globally harmonized regulatory framework for cosmetic products that recognizes the true benefits to well-being of the consumers, the excellent safety record of the industry in the past 60 years and the commitment to constantly raise the level of quality of the products,” he concludes.

Without that legislation, the industry must demonstrate responsibility by thoroughly examining the implications and effects of the ingredients and products it develops—to innovate with caution.

A High Price Tag?

The development for Mibelle’s PhytoCellTec Malus Domestica, for example, took more than three years and, therefore, was very expensive. “We also had to show the efficacy of the product regarding protection of skin stem cells,” says Fred Zülli, business unit manager, Mibelle. “Because it was a first, we had to invest quite a bit of money to get the result.” The company had to invent a new reactor type to produce the plant stem cells in a more cost-effective way than it was done before. Therefore, the initial development was very expensive, but the ongoing product is definitely affordable. It also paved the way for its Solar Vistis product and other innovations.

And while ingredients such as PhytoCellTec Malus Domestica are indeed expensive, they are within the range of other molecules and ingredients, such as peptides, used in advanced formulations. “In general, the cost of ingredients is overestimated regarding the selling price of a finished product,” explains Zülli. “The brand image (advertising cost), packaging (packaging costs) and distribution channel (margins of each step) usually are much more important for the pricing of the final product.”

Because a cosmetic product is based on the basic material—emulsion, packaging, documentation—and on an added value made up by the brand image, innovation and purchase experience, the customer is willing to pay extra for—in addition to a nice formulation, efficacy and packaging—the added value. Consumers want to see the results. “Innovation is the key success factor in cosmetics,” says Zülli.

“Our company has established an efficient innovation process to meet the demands of these markets and consumers.” Therefore, an ingredient such as Mibelle’s apple stem cells will not only add functionality to the product but will also create a new cosmetic story based on a rare Swiss apple, a new sustainable technology and a novel field such as skin stem cell protection. Despite consumer choices leaning toward less expensive items, YG Lab’s Rebecca James Gadberry agrees that they are willing to pay a higher price for natural, sustainable products that work.

YG Lab’s successful products layer results, she explains. Consumers are trained to continue use of a product with immediate results and, therefore, will experience the more long-term results. The key is for brand owners to ensure products they are selling are doing what they claim. “And the more you can prove the product will be beneficial, the more likely consumers will be to pay for it in the first place,” says Gadberry.

In time, cost reduction will make ingredients more accessible as well. The past has shown that new ingredients and concepts will move from prestige cosmetics to mass-market and private label. This transition has become much faster than in years past. Zülli explains, “About 20 years ago, liposomes maintained [a long-term, sole presence] in the prestige market before they moved into mass-market and finally disappeared from the labeling. Recent developments such as peptides moved [in positioning and segment] in less than three or four years. Therefore, we believe that PhytoCellTec and similar technologies will also be available to mass-market products in a few years, if the concept is fully understood by the consumers.” The relatively high price of the ingredient, for now, will limit this transition.